Rv2776c Resolved · high auto-curated
H37Rv Rv2776c · MTBC0 - ·
309 aa · 3083374–3084303 (-) ·
RefSeq NP_217292.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxidoreductase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Oxidoreductase. Pfam: NAD_binding_1 (PF00175.27), Fer2 (PF00111.33). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O86347
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Probable oxidoreductase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| eggNOG description | oxidoreductase |
| Orthologous group | COG1018 |
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (175) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
NAD_binding_1 | PF00175.27 | 1.1e-04 | 112–202 | Oxidoreductase NAD-binding domain |
Fer2 | PF00111.33 | 3.7e-10 | 234–300 | 2Fe-2S iron-sulfur cluster binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cyp123 (cytochrome P450 Cyp123), high confidence from genomic context alone (score 916 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0766c cyp123 |
cytochrome P450 Cyp123 | 920 | 916 ctx | fusion:740 |
Rv3518c cyp142 |
cytochrome P450 monooxygenase Cyp142 | 902 | 896 ctx | fusion:674 |
Rv2777c hyp |
hypothetical protein | 875 | 876 ctx | neighborhood:741 |
Rv1465 |
nitrogen fixation related protein | 872 | 853 | database:621 |
Rv3025c iscS |
cysteine desulfurase | 854 | 834 | experimental:422 database:621 |
Rv3121 cyp141 |
cytochrome P450 Cyp141 | 837 | 828 ctx | fusion:449 |
Rv1256c cyp130 |
cytochrome P450 Cyp130 | 829 | 819 ctx | fusion:514 |
Rv0778 cyp126 |
cytochrome P450 Cyp126 | 803 | 791 | |
Rv2266 cyp124 |
cytochrome P450 Cyp124 | 796 | 783 | |
Rv1175c fadH |
NADPH dependent 2,4-dienoyl-CoA reductase FadH | 836 | 776 | experimental:430 database:568 |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 866 | 773 | experimental:430 database:568 textmining:436 |
Rv2268c cyp128 |
cytochrome P450 Cyp128 | 770 | 756 | |
Rv3858c gltD |
glutamate synthase small subunit | 779 | 753 | experimental:430 database:568 |
Rv3106 fprA |
NADPH-ferredoxin reductase FprA | 778 | 752 | experimental:430 database:568 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 785 | 751 | experimental:700 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): oxidoreductase
- Pfam (hmmscan --cut_ga): NAD_binding_1 PF00175.27 (E=1e-04), Fer2 PF00111.33 (E=4e-10)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217292.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_1 (PF00175.27), Fer2 (PF00111.33)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG1018 - Curated reference: UniProt O86347 (TrEMBL, unreviewed; Predicted)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
97 functional partner(s); context anchor
cyp123 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2776c| MRRTNPAVVTKRELVAPDVVALTLADPGGGLLPAWSPGGHIDVQLPSGRRRQYSLCGVPGRRTDYRIAIRRIADGGGGSIEMHEAFDVGDTCEFEGPRNAFHLGLAERDVLFVIGGIGVTPILPMIRAAEQRGIDWRAIYAGRGREYMPFLDEVVAVAPGRVTVWADDEHGRFASVDELLAGAGPTTAVYVCGPPGMLEAVRVARNQHADAPLHYERFSPPPVVDGVPFELELARSRRVLRVPANRSALDVMLDWDPTTAYSCQQGFCGTCKVRVLAGQVDRRGRIIEGDNEMLVCVSRAVSGRVVIDA